The Landscape of CAR T Cells Beyond Acute Lymphoblastic Leukemia for Pediatric Solid Tumors

Adoptive cell therapywith genetically modified T cells holds the promise to improve outcomes for children with recurrent/refractory solid tumors and has the potential to reduce treatment complications for all patients. Although T cells that express chimeric antigen receptors(CARs) specific for CD19have had remarkable success for B-cell–derived malignancies, which has led to their approval by the U.S. Food and Drug Administration, CAR T cells have been less effective for solid tumors and brain tumors. Lack of efficacy is most likely multifactorial, but heterogeneous antigen expression; limited migration of T cells to tumor sites; and the immunosuppressive, hostile tumor microenvironmenthave emerged as major roadblocks that must be addressed. In this review, we summarize the clinical experience with CAR T-cell therapyfor pediatric solid tumors, including brain tumors. In addition, we review strategies that have been and are being developed to enhance their antitumor activity.